Human prostate cell lines in cancer treatment

Abstract

Combinations of cell lines are provided for allogeneic immunotherapy agents in the treatment of cancer. Cancer vaccines generally have been limited to the use of cells that contain at least some tumour specific antigens (“TSAs”) and/or tumour associated antigens (“TAAs”) having shared identity with antigens in a targeted tumour. In such cases, tumour cells often are utilised as a starting point on the premise that only tumour cells will contain TSAs or TAAs or relevance, and the tissue origins of the cells are matched to the tumour site in patients. A primary aspect of the invention is the use of immortalised normal, non-malignant cells as the basis of an allogeneic cell cancer vaccine. Normal cells do not posses TSAs or relevant concentrations of TAAs and hence it is surprising that, normal cells are effective as anti-cancer vaccines. More surprisingly, a three way combination of cells obtained from metastasised cells, non metastasised tumour and cells from a normal cell line provided good therapy. For prostate cancer, for example, a vaccine may be based on one or a combination of different immortalised normal cell lines derived from the prostate according to parameters described herein. The cell lines may be lethally irradiated with, for example, gamma irradiation at 50-300 Gy to ensure that they are replication incompetent prior to use.

1 . An allogeneic immunotherapy vaccine for the treatment of prostate cancer in a patient, comprising an adjuvant, cells from a first allogeneic normal prostate cell line, cells from a second allogeneic cell line obtained from a primary prostate cancer biopsy, and cells from a third allogeneic cell line obtained from a metastasis of prostate cancer, wherein the cells of the second allogeneic cell line exhibit tumour associated glycoprotein related to sialyated Tn antigen.  
     
     
         2 . A vaccine as described in  claim 1 , wherein the adjuvant comprises one or more of bacille Calmette-Guérin, a  Mycobacterium, Mycobacterium vaccae , Tetanus toxoid, Diphtheria toxoid,  Bordetella Pertussis , interleukin 2, interleukin 12, interleukin 4, interleukin 7, Complete Freund's Adjuvant, and Incomplete Freund's Adjuvant.  
     
     
         3 . A vaccine as described in  claim 1 , wherein the adjuvant comprises inactivated  Mycobacterium vaccae bacilli.    
     
     
         4 . A vaccine as described in  claim 1 , wherein the adjuvant comprises inactivated bacilli Calmette-Guerin.  
     
     
         5 . A vaccine as described in  claim 1 , wherein the third allogeneic cell line is derived from a prostate cancer that has metastasised to one of the lymph nodes, bone, brain and liver.  
     
     
         6 . A vaccine as described in  claim 5 , wherein the first cell line is OnyCap-23, the second cell line is P4E6 and the third cell line is LnCaP.  
     
     
         7 . A vaccine as described in  claim 5 , comprising cells from at least two cell lines derived from prostate cancers that have metastasised to one or more tissues selected from the group consisting of the lymph nodes, bone, brain and liver.  
     
     
         8 . A vaccine as described in  claim 7 , comprising cells from at least five cell lines derived from prostate cancers that have metastasised to one or more tissues selected from the group consisting of the lymph nodes, bone, brain and liver.  
     
     
         9 . A vaccine as described in  claim 6 , comprising cells from at least 2 cell lines that have been derived from primary prostate cancer biopsies.  
     
     
         10 . A vaccine as described in  claim 9 , comprising cells from at least 2 cell lines that have been derived from primary prostate cancer biopsies.  
     
     
         11 . An allogeneic immunotherapy vaccine for the treatment of prostate cancer in a patient, comprising an adjuvant, allogeneic cells from a first normal prostate cell line, allogeneic cells from a second immortalized cell line obtained from a prostate cancer biopsy, and allogeneic cells from a third immortalized line obtained from a prostate cancer biopsy.  
     
     
         12 . A vaccine as described in  claim 1 , wherein the allogeneic cells are lethally irradiated to ensure that the cells are replication incompetent.  
     
     
         13 . A vaccine as described in  claim 12 , wherein the cells are irradiated utilising gamma irradiation at 20-400 Gy.  
     
     
         14 . A vaccine as described in  claim 1 , further comprising a cryoprotectant.  
     
     
         15 . A vaccine as described in  claim 14 , wherein the cryoprotectant comprises at least one of 10-30% v/v aqueous glycerol, 5-20% v/v dimethyl sulphoxide and 5-20% w/v human serum albumin.  
     
     
         16 . A method of prophylaxis or treatment of prostate cancer, comprising providing the vaccine of  claim 1 , and administering the vaccine to a patient in a suitable dosage form.  
     
     
         17 . A method of treating a prostate cancer that has metastasised to a tissue selected from the group consisting of bone, lymph node, brain and liver, comprising administering the vaccine of  claim 1 , wherein the third allogeneic cell line of the vaccine is derived from a prostate cancer that has metastasised to the selected tissue.  
     
     
         18 . An allogeneic immunotherapy vaccine as described in  claim 17 , wherein the first allogeneic cell line is OnyCap-23.